GT70 - Abstract Preview
GT70
Symposium: S01 - General Session
Poster Presentation
 
 

Influence of PAMAM dendrimers on the human insulin

Nowacka Olga (1), Milowska Katarzyna (1), Ionov Maksim (2)*, Bryszewska Maria (1)

(1) University of Lodz, Faculty of Biology and Environmental Protection - Lodz - Poland, (2) University of Lodz, Department of General Biophysics - Lodz - Poland

Dendrimers are specific class of polymeric macromolecules. They have globular shape, consist of a central core and branched monomers. On the surface they have terminal groups or molecules that give the dendrimers the desired functions for pharmaceutical and biomedical applications. These properties give possibility to use dendrimers as drug delivery systems by attaching the drug molecule to the dendrimer or encapsulate drug molecule inside the dendrimer. They may not only be carriers of drugs, but also have therapeutic properties, which are related to their high affinity to the protein structures. One of the promising activities of dendrimers involves inhibition of protein fibril formation. Aggregation and fibrillation of insulin occurs in insulin-dependent diabetic patients after repeated administration, due to these processes being very easily triggered by the conditions of drug administration. The aim of this work was to study the interaction between PAMAM dendrimers of various generations and human insulin by measurements of dendrimers effect on zeta potential, secondary structure and thermal stability. We observed the dependence between the number of positive charges on the surface of the PAMAM dendrimer and the values of zeta potential. Addition of dendrimers to insulin caused insignificant changes in the secondary structure. There was a small decrease in ellipticity, but it did not result in alterations in the circular dichroism (CD) spectrum shape. Thermostability of human insulin was studied using differential scanning calorimetry (DSC). DSC thermogram showed two phase transitions for insulin at 600C and at 820C. After the addition of dendrimers in the concentration of 0.06 μmol/l the first peaks disappeared and the second peaks became higher. We suppose that the presence of dendrimers the induced the transformation of dimers into hexamers. The work was supported by the grant UMO-2012/04/M/NZ1/00059